Acute Exercise and NK Cell Regulation in Tissue and Circulation After IL-6R Blockade

NCT04616235 | Completed

• 1 other identifier: jr. nr. H-20028611
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

The study is a randomized controlled trial studying the acute effect of intense aerobic exercise upon NK (Natural Killer) cell activation and appetite-regulation in human participants with or without concommitant IL-6R receptor blockade (Tocilizumab)

Conditions

Interleukin-6 Inhibition; Physical Stress; Appetitive Behavior

Keywords

Natural Killer cells; Aerobic exercise; IL-6R blockade; Human; Appetite

Outcome Measures

Primary Outcomes (2)

• Kinetics and regulation of NK (Natural Killer) cells during and following acute exercise

  Change in NK cell and NK cell subset count in circulation before and after acute aerobic exercise with or without IL-6R blockade.

  Up to 1 day

• NK cell phenotype in response to acute exercise with or without IL-6R blockade

  Change in NK-cell phenotype using single cell RNA sequencing. Here, within-group changes of baseline vs. post exercise timepoints as well as between group differences between IL-6 blockade and placebo will be investigated. The focus will be on markers of cytotoxicity, cell adhesion and adrenergic signaling.

  Up to 1 day

Secondary Outcomes (56)

• Change in NK cell count in adipose tissue

  3 hours after intervention

• Change in NK cell phenotype in adipose tissue

  3 hours after intervention

• Change in NK cell count in muscle tissue

  3 hours after intervention

• Change in NK cell phenotype in muscle tissue

  3 hours after intervention

• Change in macrophage count in muscle tissue

  3 hours after intervention

Study Arms (2)

CON

PLACEBO COMPARATOR

This group will do intense aerobic exercise without concomitant IL-6R blockade

Other: Saline 0.9% 100 ml NaCl 0.9% will be infused over 1 hour

BLOCK

ACTIVE COMPARATOR

This group will do intense aerobic exercise with concomitant IL-6R blockade

Drug: Tocilizumab Injectable Product

Interventions

Tocilizumab Injectable Product DRUG

The intervention group will undergo intense aerobic exercise with prior IL-6R infusion for 1h prior to the exercise bout.

BLOCK

Saline 0.9% 100 ml NaCl 0.9% will be infused over 1 hour OTHER

The control group will undergo intense aerobic exercise with saline infusion for 1h prior to the exercise bout

CON

Eligibility Criteria

• Age: 18 Years - 40 Years
• Gender Eligibility Details: Participants will have to be biological males since hormonal fluctuations in women might have unknown effects on immune cell regulation during acute intense exercise
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• recreationally active
• moderately trained
• healthy young males aged 18-40 years
• BMI from 18-30 kg·m2

You may not qualify if:

• Cardiovascular disease
• Rheumatologic disease
• Metabolic disease,
• Elite sports or high aerobically training status (VO2max\>60ml O2/min/kg),
• Frequent/chronic use of medications affecting physical performance or inflammation (NSAIDS, DMARDS)

Sponsors & Collaborators

• Rigshospitalet, Denmark: lead

Study Sites (1)

Center For Physical Activity (CFAS)

Copenhagen Ø, 2100, Denmark

Location

Related Publications (42)

• Amar, D., Lindholm, M. E., Norrbom, J., Wheeler, M. T., Rivas, M., & Ashley, E. A. (2020). Differential Response Trajectories to Acute Exercise in Blood and Muscle. SSRN Electronic Journal, 1-43. https://doi.org/10.2139/ssrn.3508810

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MeSH Terms

Conditions

Appetitive Behavior

Interventions

Sodium Chloride

Condition Hierarchy (Ancestors)

Behavior, Animal; Behavior

Intervention Hierarchy (Ancestors)

Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Study Officials

• Andreas K Ziegler, PhD

  CFAS (Center For Physical Activity) Rigshospitalet

  PRINCIPAL INVESTIGATOR

• Jesper F Christensen, PhD

  CFAS (Center For Physical Activity) Rigshospitalet

  PRINCIPAL INVESTIGATOR

• Claus Brandt, PhD

  CFAS (Center For Physical Activity) Rigshospitalet

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: The IL-6R receptor blockade infusion will have bag concealment so that neither the scientific staff or the subject will know if Tocilizumab or saline (placebo) is given and we do not expect the subjects to "feel" the infusion or the results of the infusion. All scientific staff will be blinded to group allocation using encryption. Only once all data have been obtained (histology, blood analysis, gene-expression, Western Blot, Flow cytometry, single cell RNA sequencing) concealment will be broken so that statistical analysis can be conducted.
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: October 20, 2020
• First Posted: November 4, 2020
• Study Start: March 15, 2021
• Primary Completion: October 4, 2021
• Study Completion: October 4, 2021
• Last Updated: August 22, 2022

Record last verified: 2022-08

Data Sharing

• IPD Sharing: Will not share

Locations

DK (1)